Goel R, Varma S, Kaul D
Department of Experimental Medicine and Biotechnology, Chandigarh, India.
Cancer Lett. 1996 Oct 22;107(2):193-8. doi: 10.1016/0304-3835(96)04355-8.
Sterol regulatory element (SRE) has been recognized to regulate various key genes coding for especially low density lipoprotein (LDL)-receptor, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and HMG-CoA synthase known to play a crucial role in the cholesterol feedback mechanism. The deranged cholesterol feedback mechanism has been widely recognised in initiation as well as progression of various types of cancers including chronic myeloid leukaemia (CML). Consequently, the present study was addressed to understand this phenomenon and revealed the existence of a unique 47 kDa protein factor having affinity for this SRE sequence in lymphocytes from normal subjects as well as its absence in lymphocytes from untreated CML patients. However, this factor appeared when the CML patients achieved complete haematological remission (CHR) through alpha-interferon therapy. Further, an inverse relationship was also observed between sterol modulated LDL-receptor gene transcription and the binding affinity of this 47 kDa factor to the SRE sequence. Based upon these results we propose that alpha-interferon through its receptor initiates phosphatidic acid dependent signalling which in turn regulates the affinity of 47 kDa sterol regulatory element binding factor as well as LDL-receptor gene transcription in lymphocytes from CML patients.
固醇调节元件（SRE）已被确认可调节多种关键基因，这些基因编码的蛋白质在胆固醇反馈机制中发挥关键作用，尤其是低密度脂蛋白（LDL）受体、3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶和HMG-CoA合酶。在包括慢性髓性白血病（CML）在内的各种癌症的发生和发展过程中，紊乱的胆固醇反馈机制已得到广泛认可。因此，本研究旨在了解这一现象，并揭示正常受试者淋巴细胞中存在一种对该SRE序列具有亲和力的独特47 kDa蛋白质因子，而未经治疗的CML患者的淋巴细胞中则不存在这种因子。然而，当CML患者通过α-干扰素治疗实现完全血液学缓解（CHR）时，这种因子会出现。此外，还观察到固醇调节的LDL受体基因转录与这种47 kDa因子与SRE序列的结合亲和力之间存在负相关关系。基于这些结果，我们提出α-干扰素通过其受体启动磷脂酸依赖性信号传导，进而调节CML患者淋巴细胞中47 kDa固醇调节元件结合因子的亲和力以及LDL受体基因转录。
